This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HYPOTHESIS I. The prospective collection of data on a large cohort of premature infants with necrotizing enterocolitis (NEC) will accurately define the natural history of this devastating disease. These data will also permit definition of risk factors for developing severe NEC and the outcome of current practices in the treatment of NEC. II. SPECIFIC AIMS Specific Aim 1: To determine the risk factors for patients with NEC to progress to perforation or necrosis requiring surgical intervention. Specific Aim 2: To determine the relationship between feeding practices and the progression of NEC. Specific Aim 3: To determine the relationship between feeding regarding type and duration of antibiotic therapy in patients with non-surgical NEC in order to determine its impact on disease progression. Specific Aim 4: To determine the disease and patient specific factors that predict the occurrence of long-term nutritional deficiency and gastrointestinal disease. III. BACKGROUND AND SIGNIFICANCE Pediatric surgeons often care for children with uncommon diseases. This is particularly true of major neonatal surgical disorders such as Necrotizing Enterocolitis (NEC). Even a major pediatric referral center will not see an adequate number of patients to meaningfully assess outcomes from the institution's treatment approach. For this reason, the scientific literature on the care of children with NEC is almost exclusively comprised of anecdotal case reports and single-institution case-series data. The Glaser Research Network was established in 2001 to coordinate data collection between 6 institutions (Baylor, Harvard, University of San Francisco, Stanford, USC, UCLA). By combining data from these 6 institutions on infants with NEC a more meaningful analysis can be carried out. Necrotizing Enterocolitis is a severe inflammatory disease of the intestine that occurs in premature and low birth weight infants. First described in the 1060's, NEC is now the most common surgical emergency in the newborn infant. The incidence of NEC is reported to be from 1% to 5% of neonatal intensive care unit (NICU) admissions or 1 to 3 cases per 1,000 live births. Based upon analysis of data from the National Center for Health Statistics and multi-center trials, there are about 10,000 cases of NEC per year in the United States. This results in approximately 2500 deaths per year. The incidence of NEC correlates strongly with the degree of prematurity. It is these very low birth weight babies that present the physician with the greatest clinical challenge. Since successful treatment of NEC typically results in the child being able to lead a healthy and fully productive life, improvements in care can produce a tremendous impact in terms of number of years of life saved. The clinical presentation of NEC can range from feeding intolerance to severe sepsis with cardiovascular collapse. No definitive treatment for NEC exists. Most cases respond to discontinuation of oral feedings with nasogastric decompression, fluid resuscitation, broad-spectrum antibiotics, and other supportive measures. Severe NEC can result in intestinal necrosis and perforation. When these conditions occur, surgical intervention is necessary. Once the diagnosis of NEC is made, standard of practice is to institute bowel rest, gastric decompression, and broad spectrum antibiotics. Many patients respond well to this treatment and recover with no further intervention. Others deteriorate and develop intestinal necrosis or perforation requiring urgent operation. There is little available evidence to suggest what factors may help predict which infants are most likely to deteriorate. To date, no large prospective studies have followed infants diagnosed with NEC and determined their course. Identification of risk factors for deterioration could allow more intensive therapy to be focused on those most likely to benefit. In addition, such data could allow a more rapid return to enteral feeding and routing neonatal care for those not at high risk.